STROMA Sintesi della relazione

Final Report Summary - STROMA (Selective targeting of angiogenesis and of tumor stroma)

Many cancer types remain incurable; there is an urgent need to harness the fruits of technological advances in chemistry and biology for the discovery of better therapeutic agents. The STROMA project has allowed to make progress in cancer therapy, with considerable potential therapeutic benefit to patients with cancer and the competitiveness of the European pharmaceutical industry.

From the very beginning, the primary goal of the STROMA project was clearly defined as the development of selective and efficacious anti-cancer therapeutics, by means of the targeted delivery of potent bioactive moieties to the tumour-associated antigens, located in the neo-vasculature and / or the tumour stroma, thus sparing normal tissues.

At the end of the STROMA project, a positive balance can be drawn. While STROMA activities ended with the preparation for clinical trials (and did not include clinical studies), the fact that the following products have entered industrial and clinical development is evidence of the scientific and technological progress made. It is worth mentioning that at the beginning of the project, we declared that we would consider the project as truly successful if at least one compound, developed within the framework of this project, would have entered serious clinical and industrial development programs in the field of oncology.

The structure of the project followed the natural flow in the development of novel antibody-based therapeutics. Starting from target identification (i.e. the discovery of proteins which are over-expressed at neovascular sites and in the stroma of neoplastic lesions), the project progressed to the generation and validation of human monoclonal antibodies specific to these targets; this step has been followed by the engineering of judiciously selected antibodies into biopharmaceuticals and their evaluation in animal models of cancer.

As some good-quality monoclonal antibodies were available at the beginning of the STROMA project (e.g. the L19 antibody, specific to the EDB domain of fibronectin, a marker of angiogenesis), these reagents could directly be used for the investigation of strategies for the engineering of antibodies into anti-cancer agents. Other targets were discovered during the carrying over of the project and were moved through the development pathways thanks to the generation of new human monoclonal antibodies.